2-222297158-G-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_181458.4(PAX3):c.141C>G(p.Asn47Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N47H) has been classified as Pathogenic.
Frequency
Consequence
NM_181458.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Craniofacial-deafness-hand syndrome Pathogenic:1
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not provided Pathogenic:1
Identified in a family with craniofacial-deafness-hand syndrome in published literature (Sommer and Bartholomew, 2003); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 8664898, 6859126, 27013732, 14556253) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at